This invention was made in the performance of work under a grant from the National Institute of Health #HL 16,796; AN 10,628; and BRSG S07RR-05583-25 and the U.S. Government has certain rights therein.
1. Field of the Invention
The invention provides a novel method using a group of compounds to modulate biological activities comprising sulfur-containing hydrocarbon derivatives of carboxy-amino-amides such as vitaletheine, [N-(2-mercapto-ethane)-3-carboxyamino-propanamide], also designated as N-[3-(2-mercapto-ethanamino)-3-oxo-3,1-propanediyl]-carbamic acid, herein referred to as "vitaletheine modulators". The compounds are characterized by a pronounced biological activity, and are useful, inter alia, for reestablishing the normal phenotypic expression of neoplastic cells in vivo and in vitro, and for stimulating immunological surveillance for neoplastic cells. In particular, the compounds inhibit tumor growth, inhibit metastasis of tumor cells, and regress tumors.
"Phenotypic expression" is defined herein as the manifestation of an "entire range of physical, biochemical and physiological characteristics of an individual as determined both genetically and environmentally," in contrast to "genotypic expression", which in the art solely refers to the expression of the chromosomal sequence. [See, for example, Dorland's Illustrated Medical Dictionary, 26th Edition, 1974, W. B. Saunders, Philadelphia]. Biological activity of the vitaletheine modulators thus includes modulation of the expression of genetic material as influenced by the condition and environment of each cell.
2. Discussion of Related Art
Cancer (neoplasia) is popularly treated with chemotherapeutics, debulking, and/or radiotherapeutics, the efficacy of which is primarily dependent upon differences in growth rates between normal and neoplastic cells. These therapies have proven to be marginally effective. More recent therapies have sought to fortify bodily defenses against developing tumors, for example by enhancing immunological responses of the body postulated to be belligerent to neoplastic cells. Only in part due to the complexity of the immune system, such therapies have not as yet proven their value. There is circumstantial evidence that NK (natural killer) cells may be important effector cells against tumor development in the early stages as described in Immunobiology of Natural Killer Cells, volumes I and II, 1986, CRC Press, Inc., Boca Raton, Fla., U.S.A., incorporated herein by reference. There is also evidence that through adoptive immunotherapy (the removal, in vitro activation, and return of immunologically reactive lymphoid cells to the afficted animal) the regression of established tumors in the animal can be mediated as described in Immune Responses to Metastases, volumes I and II, 1987, Boca Raton, Fla., U.S.A., incorporated herein by reference. It is accordingly desirable to provide a method for normalizing cellular function to interrupt underlying mechanisms of cellular transformation to neoplastic cells, and to identify and enhance, either in vivo or in vitro, those biological responses antagonistic towards neoplastic cells.